Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task

Eric J. Nunes, Patrick A. Randall, Alexavier Estrada, Brian Epling, Evan E. Hart, Christie A. Lee, Younis Baqi, Christa E. Müller, Mercè Correa, John D. Salamone

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Abstract

Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

Original languageEnglish
Pages (from-to)727-736
Number of pages10
JournalPsychopharmacology
Volume231
Issue number4
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Accumbens
  • Adenosine
  • Anergia
  • Depression
  • Fatigue
  • Motivation

ASJC Scopus subject areas

  • Pharmacology

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    Nunes, E. J., Randall, P. A., Estrada, A., Epling, B., Hart, E. E., Lee, C. A., Baqi, Y., Müller, C. E., Correa, M., & Salamone, J. D. (2014). Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: Studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology, 231(4), 727-736. https://doi.org/10.1007/s00213-013-3285-4